This research proposal is being initiated for the purpose of examining the problem of the regulation of gene expression by sex hormones in embryonic and adult target tissues. Three specific approaches to the problem will be undertaken. First, a cell-free protein synthesizing system that is dependent on the in vitro addition of sex hormone will be developed as a model system that can be used to dissect the molecular basis of sex hormone action. This system will be based on the estrogen-induced synthesis of phosvitin by rooster liver. Second, to help resolve the complex sequence of events in androgen regulation of gene activity, a genetic analysis of mutants exhibiting defective androgen action will be carried out. Cultured human cells derived from patients with genetic forms of androgen insensitivity and human somatic cells with conditional lethal mutants isolated by temperature sensitivity will be utilized. Finally, a series of biochemical genetic studies on the process of embryonic sexual differentiation will be initiated in order to gain a better understanding of how androgens activate genes during the differentiation of the genital tract. BIBLIOGRAPHIC REFERENCES: Brown, M.S., and Goldstein, J.L.: New directions in human biochemical genetics: Understanding the manifestations of receptor deficiency states. Progress in Medical Genetics. (Second Series) 1: 103-119, 1976. Brown, M.S., and Goldstein, J.L.: Receptor-mediated control of cholesterol metabolism. Science. 191: 150-154, 1976.